LitCovid-sentences  

PMC:7354481 / 24249-45823 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T164 0-4 Sentence denotes 4.1.
T165 5-57 Sentence denotes Biological Significance of Top Ranked miRs in Humans
T166 59-74 Sentence denotes 4.1.1. miR-8066
T167 75-192 Sentence denotes Recently, the N nucleocapsid gene-related putative miR candidates were shown through in silico prediction tools [38].
T168 193-341 Sentence denotes In a similar manner, we determined miR-8066, a mature sequence found on SARS-CoV-2 genomes, in SARS-CoV-2 genome alignment analysis with human miRs.
T169 342-505 Sentence denotes Additionally, miR-8067, which possesses a similar biological role to miR-8066, was identified as a stem loop region sequence in all SARS-CoV-2 genomes (Figure S1).
T170 506-627 Sentence denotes Previous reports showed that both miRs are found in plasma samples of sepsis patients with severe clinical outcomes [39].
T171 628-766 Sentence denotes Similar miR family members such as miR-8054, miR-8057, miR-8061, and miR-8068, were also found in a non-survivor group of sepsis patients.
T172 767-899 Sentence denotes It has been shown by in silico analysis that certain miRNAs have the core motifs of AUUGUUG, and that miR-8066 is one of these [40].
T173 900-1132 Sentence denotes When miRs have this motif, it increases their likelihood to bind and activate Nf κB-mediated TLR-8 expression and induce cytokine synthesis [40]. miR-8066 was identified at high levels in tissue biopsies as well as in exosomes [41].
T174 1133-1322 Sentence denotes Therefore, SARS-CoV-2-mediated alterations of miRs may act as autocrine or paracrine agonists of host cells to trigger pro-inflammatory cytokines, due to their increased NfKB activity [42].
T175 1323-1453 Sentence denotes Similar findings were also suggested for cancer cells, which showed miR alterations in association with inflammation markers [43].
T176 1454-1638 Sentence denotes There is preliminary data about the existence of sequence similarity of human miRs in the spike region of the SARS-CoV-2 genome for both forward and reverse complementary strands [44].
T177 1639-1779 Sentence denotes Hsa-miR-8055, which was also previously shown to be a sepsis marker, was found to be involved in T-cell responses to specific antigens [45].
T178 1780-2021 Sentence denotes One of the differentially expressed circRNAs in children with fulminant myocarditis, Circ_0071542, was suggested to regulate the expression of MAPK, a well-characterized target in the development of disease through binding hsa-miR-8055 [45].
T179 2022-2275 Sentence denotes In our current study, we found that the miR-8066 sequence is present in four different SARS-CoV-2 genomes and shows strong association in KEGG pathways for TGF-beta signalling, mucin type O-glycan biosynthesis and cytokine-cytokine receptor interaction.
T180 2276-2437 Sentence denotes These targeted pathways are known, critical mediators for the clinical outcomes for SARS-CoV-2-infected patients and give us insight about virus pathophysiology.
T181 2438-2649 Sentence denotes It is well established that for enveloped viruses, such as SARS-CoV-2, N- or O-glycosylation of S protein determines the viral entry and membrane fusion with functional elicitation of host immune responses [46].
T182 2650-2821 Sentence denotes The high-resolution LC-MS/MS experiment was performed to detect site-specific quantitative N-linked and O-linked glycan profiling on SARS-CoV-2 subunit S1 and S2 proteins.
T183 2822-2985 Sentence denotes The glycan profiling showed that two unexpected O-glycosylation sites on the receptor-binding domain (RBD) of subunit S1 increased the pathogenicity of SARS-CoV-2.
T184 2986-3179 Sentence denotes Therefore, our understanding of complex sialylated N-glycans and sialylated mucin type O-glycans on the functional RBD domain may help to evaluate better therapeutic or vaccine strategies [47].
T185 3180-3319 Sentence denotes Moreover, miR-8066 alters N-glycosylation patterns according to the microT-CDS pathway and may have biomarker potential for this mechanism.
T186 3320-3516 Sentence denotes In addition, miR-8066 is found to be associated with one of the critical clinical problems of COVID-19, the cytokine storm, owing to its potential effect on the cytokine-cytokine receptor pathway.
T187 3517-3680 Sentence denotes It is well established that miR-8066 affects PRLR, CXCL6, IL6, IL17 and ACVR1 target genes, which are crucial members of the cytokine regulatory network (Table 2).
T188 3681-4123 Sentence denotes According to previous NGS platform results obtained from healthy versus SARS-CoV-2-infected lung tissue biopsies (Bioproject PRJNA615032), the most highly upregulated pathways are chemokine binding receptors (p value 7.94 × 10−4), FGFR activation pathways (p value 0.002) and its downstream pathway (p value 0.001), neutrophil degranulation (p value 0.003), and IL10 (p value 0.005), when compared with normal lung tissue biopsies (Table S2).
T189 4124-4324 Sentence denotes On the contrary, according to the REACTOME pathway analysis of Bioproject PRJNA615032 data, neutrophil degradation was also downregulated in SARS-CoV-2-infected biopsy specimens (p value 1.74 × 10−6).
T190 4325-4660 Sentence denotes Briefly, the downregulation of host cell responses’ related pathway members such as SRP-dependent co-translational protein targeting to membrane, L13a-mediated translational silencing of ceruloplasmin expression antigen processing, ribosomal organization, and the ERAD pathway, were observed in COVID-19-positive lung biopsy specimens.
T191 4661-4867 Sentence denotes All of these preliminary gene expression differences, between normal and SARS-CoV-2-infected lung biopsies, are associated with detected miR pathways and highlight common clinical presentations of patients.
T192 4868-5100 Sentence denotes Each of these biological mechanisms, according to potential disease progression-related alterations in the host genome, is highly associated with TGF-β, which is a cytokine affecting a number of host responses during infection [48].
T193 5101-5243 Sentence denotes TGF-β mediates the immune responses of host cells, as well as altering tissue remodelling by affecting cell survival, apoptosis and migration.
T194 5244-5507 Sentence denotes It has been demonstrated that SARS-CoV N protein potentiate Smad-3 mediated TGF-β activation, and plasminogen activator inhibitor-1 (PAI-1), leading to severe pulmonary fibrosis and inactivation of pro-apoptotic genes by complex formation of Smad3 and Smad4 [48].
T195 5509-5524 Sentence denotes 4.1.2. miR-5197
T196 5525-5649 Sentence denotes miR-5197-3p was identified as the most effective miR to interact with the guide RNA of SARS-CoV, MERS-CoV and COVID-19 [49].
T197 5650-5909 Sentence denotes According to a recent study, out of 2565 miRNAs, only three critical miRs, 5197-3p, 4778-3p and 6864-5p could interact with complete complementary miR (cc-miR) and possess a critical therapeutic potential due to their binding affinity on SARS-CoV-2 guide RNA.
T198 5910-6151 Sentence denotes It was suggested that the generation of miR-5197-3p-based complete complementary miRNA may possess a significant therapeutic response, owing to its structural affinity to guide RNA of SARS-CoV-2, without any side effects on human genes [49].
T199 6152-6309 Sentence denotes Previous patents on hsa-miR-5197-5p indicated that any drug targeting this miR might be critical in the treatment of hepatitis B infections (WO2018193902A1).
T200 6310-6468 Sentence denotes Similar to this finding, it was shown that miR-5197-3p might be used in vaccine strategies in the herpes simplex virus (HSV-1) (WO2013109604A1WO2013109604A1).
T201 6469-6601 Sentence denotes In another study, allelic variances of hsa-miR-5197 were found to be highly associated with non-small cell lung cancer (NSCLC) [50].
T202 6602-6801 Sentence denotes According to the Harvard and MD Anderson databases, miR-5197 shows significant differences between Caucasians and Chinese populations (data gained from a Han Chinese cohort from Nanjing, China) [50].
T203 6802-6910 Sentence denotes The rs2042253 polymorphism (T>C variation) of miR-5197 provided a protective effect on lung cancer survival.
T204 6911-7044 Sentence denotes Moreover, this SNP is reported to have a high read frequency for paediatric acute lymphoblastic leukemia (ALL) in the UK cohort [51].
T205 7045-7200 Sentence denotes High throughput analysis of 408 lung cancer patients showed that miR-5197 polymorphism is highly correlated with chemotherapy-induced severe toxicity [52].
T206 7201-7392 Sentence denotes It has been accepted that nucleotide variations in pre-miRNAs may have contributed to the stability of stem-loop structure and may affect recognition sites for Drosha and Dicer cleavage [53].
T207 7393-7607 Sentence denotes In our current study, we did not find any mutations in miR-5197 sequences obtained from different SARS-CoV-2 genomes, however we found that mucin type O-glycan biosynthesis was related to both miRs 5197-3 and 8066.
T208 7608-7781 Sentence denotes This KEGG pathway has been involved in the cell-to-cell transmission of human T cell leukemia virus type 1 (HTLV-1) [54] and plays roles in Ebola virus cell attachment [55].
T209 7782-7899 Sentence denotes HIV-1 infection of T cells has also been shown to result in altered glycosylation of cell surface glycoproteins [56].
T210 7900-7950 Sentence denotes O-glycans are also linked to avian influenza [57].
T211 7951-8046 Sentence denotes Mucosal O-linked glycans are furthermore associated with herpes simplex virus 1 infection [58].
T212 8047-8191 Sentence denotes Mucin type O-glycan biosynthesis miR pathways have been identified in avian oncogenic retrovirus (Avian leukosis virus subgroup J (ALV-J)) [59].
T213 8192-8385 Sentence denotes This KEGG pathway is therefore related both to human as well as veterinary viral infections and further studies will be needed to establish the function of miR-5197 during SARS-CoV-2 infection.
T214 8387-8402 Sentence denotes 4.1.3. miR-3611
T215 8403-8515 Sentence denotes In our current study, we found that miR-3611 is a positive hit for stem loop region and mature miRNA prediction.
T216 8516-8704 Sentence denotes Because of its potential presence in SARS-CoV-2-mediated cellular responses, we have analysed data from the lung tissue biopsy database (PRJNA615032 Bioproject) to understand its function.
T217 8705-8804 Sentence denotes A previous study reported altered miRNA expression in chronic obstructive pulmonary disease (COPD).
T218 8805-8909 Sentence denotes COPD is an airway disorder and respiratory disease that is associated with persistent inflammation [60].
T219 8910-9068 Sentence denotes A study on miR expression analysis, conducted on COPD and healthy volunteers, showed significant down-regulation of miR-3611 expression in COPD patients [61].
T220 9069-9162 Sentence denotes The long non-coding RNA, H19, has been linked to many carcinomas, including lung cancer [62].
T221 9163-9372 Sentence denotes It has been shown that miR-3611 is significantly down-regulated in a H19 knockdown lung cancer cell line (SPC-A1), which indicated overexpression of this miR in ‘normal’ H19 intact lung cancer cell lines [63].
T222 9373-9527 Sentence denotes In our study, we identified that miR-3611 shows high similarity with all four main SARS-CoV-2 genomes and we did not detect any mutations between genomes.
T223 9528-9680 Sentence denotes However, miR-3611 was strongly associated with KEGG pathways for metabolism of xenobiotics by cytochrome P450, morphine addiction and GABAergic synapse.
T224 9681-9772 Sentence denotes Moreover, morphine addiction was, besides linkage with miR-3611, also linked to miR-5197-3.
T225 9773-9963 Sentence denotes This KEGG pathway has been related to enhanced HIV-1 infection [30] and morphine treatment has been shown to promote HIV-1 replication in macrophages via inhibition of the TLR9 pathway [64].
T226 9964-10084 Sentence denotes Furthermore, an increased rate of HIV-1/HTLV-I infection has been observed due to morphine in injection drug users [65].
T227 10085-10179 Sentence denotes Morphine is also associated with enhanced hepatitis C virus (HCV) replicon expression [66,67].
T228 10180-10413 Sentence denotes Opioids have furthermore been shown to enhance simian acquired immunodeficiency syndrome (SAIDS) in rhesus monkeys [68], while reduced clearance of pulmonary influenza virus infection was observed in morphine-treated Lewis rats [69].
T229 10414-10602 Sentence denotes Interestingly, opioids such as morphine are also used as indirect antitussives to suppress cough, which is commonly associated with respiratory viral infections [70], including SARS-CoV-2.
T230 10603-10778 Sentence denotes Indeed, morphine was used in recent cases in China during sedation and analgesia for endotracheal intubation, to avoid patients’ cough and agitation during the procedure [39].
T231 10779-10927 Sentence denotes In light of the association of morphine with promotion of viral replication, it may have effects in SARS-CoV-2 that need to be further investigated.
T232 10929-10947 Sentence denotes 4.1.4. miR-3934-3p
T233 10948-11205 Sentence denotes miRNA expression profiles have been used to classify cancers into various subtypes. miR3934 is found upregulated in colon cancer and was suggested as a biomarker for lung cancer as its expression correlated with survival rate and prognosis of NSCLC [71,72].
T234 11206-11318 Sentence denotes Moreover, it has been reported that miR-3934-5p expression significantly increases in NSCLC cell line A549 [73].
T235 11319-11465 Sentence denotes It is also a SNP linked to TGF-β signalling and has been identified as downregulated in rectal carcinoma mucosa, compared with normal mucosa [74].
T236 11466-11540 Sentence denotes In addition, it was shown that miR-3934-3p downregulated TGFBR1 and SMAD3.
T237 11541-11641 Sentence denotes In a similar vein, HSV-1 viral infection led to a significant down-regulation of these targets [74].
T238 11642-11777 Sentence denotes Moreover, the activation of the TGF-β/Smad pathway is critical for lung fibrosis, which was previously shown in SARS-CoV-related cases.
T239 11778-11900 Sentence denotes Dysregulation of ACE2 may influence the toll-receptor signalling pathway, via IL6, and affect downstream immune responses.
T240 11901-12062 Sentence denotes Irrespective of SARS-CoV-2 or pneumonia in TCGA-LUAD, the altered immunoreaction was the primary cause (lung adenocarcinoma; SARS-CoV-2; ACE2; miR-125b-5p; IL6).
T241 12063-12269 Sentence denotes TGF-β and cigarette smoke have been shown to suppress miR-141-5p to promote CCR5 expression on primary bronchial epithelial cells, which results in increased viral entry and infection by R5-tropic HIV [75].
T242 12270-12539 Sentence denotes Given that TGF-β signalling is upregulated by trans-activator (Tat) protein, cigarette smoke and in chronic lung diseases, it has been determined the effects of persistent TGF-β signalling on HIV infection in primary bronchial epithelium re-differentiated ex vivo [75].
T243 12540-12750 Sentence denotes In our current study, miR-3934-3p was found to be associated with KEGG pathways for glycosaminoglycan biosynthesis heparan sulfate/heparin, mucin type O-glycan biosynthesis and vitamin digestion and absorption.
T244 12751-12797 Sentence denotes The relevance of these pathways is as follows:
T245 12798-12887 Sentence denotes “Glycosaminoglycan biosynthesis—heparan sulfate/heparin” was here related to miRs 3934-3.
T246 12888-13038 Sentence denotes Heparan sulfate proteoglycans have previously been identified to provide the binding sites for SARS-CoV-2 invasion at the early attachment phase [76].
T247 13039-13163 Sentence denotes Furthermore, human coronavirus NL63 has been shown to utilise heparan sulfate proteoglycans for target cell attachment [77].
T248 13164-13320 Sentence denotes This KEGG pathway has been related to Ebola virus, where heparan sulfate has been identified as an important mediator in polarised epithelial cells [78,79].
T249 13321-13587 Sentence denotes In hepatitis C viral infection, the virus hijacks this pathway via interaction with apolipoprotein E for cell entry [63], while heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection [70].
T250 13588-13779 Sentence denotes Endogenous HERV-K furthermore binds to heparin for cell entry [80], and, while heparin has been found to further Zika virus infection, it acts as an antiviral against Dengue replication [81].
T251 13780-14085 Sentence denotes Heparin sulphate is identified as an inhibitory regulator of porcine epidemic diarrhoea virus infection [82] and acts as an attachment factor for rabies virus entry and infection [83], as well as an enhancer of Nipah and Hendra virus infections, which are highly pathogenic, zoonotic paramyxoviruses [84].
T252 14086-14194 Sentence denotes This highlights the importance of this KEGG pathway both in human, zoonotic and veterinary viral infections.
T253 14195-14294 Sentence denotes Another important pathway, vitamin digestion and absorption, was found to be related to miR-3934-3.
T254 14295-14425 Sentence denotes This KEGG pathway has been highlighted amongst others as a link between dysbiosis of the gut microbiome and chronic diseases [85].
T255 14426-14593 Sentence denotes Furthermore, intestinal triglyceride-rich lipoproteins have been related to vitamin metabolism in relation to coronary artery disease as well as viral infections [86].
T256 14594-14745 Sentence denotes In AIDS, malabsorption of vitamin 12 has been related to gastric secretory failure, including chronic diarrhoea, due to advanced HIV infection [87,88].
T257 14746-14840 Sentence denotes Additionally, vitamin A deficiency has been associated with more progressive HIV disease [89].
T258 14841-15025 Sentence denotes Veterinary viral infections, such as infectious bronchitis virus (IBV) and reovirus (RV) in chickens, have been identified to affect vitamin A metabolism due to epithelial damage [90].
T259 15026-15138 Sentence denotes Interestingly, a link between vitamin D deficiency and SARS-CoV-2 infection severity was recently reported [91].
T260 15139-15338 Sentence denotes Also, vitamin B3 was found to be highly effective to help lung tissue damage repair [92] and it was suggested to be given to COVID-19 patients as soon as the CT lung abnormalities were detected [93].
T261 15340-15358 Sentence denotes 4.1.5. miR-1307-3p
T262 15359-15527 Sentence denotes miR-1307 has previously been shown to be one of the lung-tissue-associated miRs [94] and was reported as an especially important target in lung development in newborns.
T263 15528-15705 Sentence denotes Expression of mir-1307-3p has furthermore been linked to acid metabolism in response to aspirin in human cardiac and peri-cardiac fat-derived mesenchymal stem cells (MSCs) [95].
T264 15706-15956 Sentence denotes Moreover, it was shown that several miRs, including miR-1307-3p, are involved in TGF-β and semaphorin signalling, as well as inflammatory responses. miRs play an important role, especially during lung morphogenesis in the early stages of development.
T265 15957-16074 Sentence denotes Interestingly, miR-1307 has been associated with the severity of pulmonary hypertension in systemic scleroderma [96].
T266 16075-16393 Sentence denotes Persistent problems with SARS-CoV-2-infected patients, such as oxygen dependency, urgent need for mechanical ventilation, persistent wheezing, and increased risk for pulmonary infections correlate with involvement of miR-1307-3p, as indicated above, due to its role in pulmonary hypertension and chronic lung diseases.
T267 16394-16612 Sentence denotes The TGF-β superfamily plays critical roles in pre- and postnatal lung development, importantly shaping alveolarisation and controlling the extracellular matrix composition and tissue homeostasis, among other functions.
T268 16613-16716 Sentence denotes TGF-β signalling is therefore strongly linked to both pulmonary and cardiovascular diseases [97,98,99].
T269 16718-16736 Sentence denotes 4.1.6. miR-3691-3p
T270 16737-16924 Sentence denotes It has been shown that oxidative stress, which has detrimental effects on intercellular communication, plays an important role in many lung pathologies such as acute lung injury and COPD.
T271 16925-17088 Sentence denotes A proteomic profile of exosomes from human bronchial epithelial cells, under normoxia and hypoxia, has reported reduced expression of miR-3691-3p in hypoxia [100].
T272 17089-17249 Sentence denotes Interestingly, miR3691-3p targets several cell signalling pathways, such as TGF-β signalling, FGF2 and also VCAM1, which is relevant for lung injury and repair.
T273 17250-17428 Sentence denotes In the current study, we have also identified that miR3691-3p exists in four of the genomes, which we have extensively studied here, and therefore it seems to be a conserved miR.
T274 17430-17447 Sentence denotes 4.1.7. miR1468-5p
T275 17448-17664 Sentence denotes Sudden cardiac death is a major problem amongst the unexplained deaths in COVID-19, and it has been identified that many of those patients suffered from primary myocardial fibrosis (PMF), without any known aetiology.
T276 17665-17960 Sentence denotes Recently, higher expression of miR-1468-3p was identified as a disease-associated and age-dependent cardiac biomarker, as it promotes cardiac fibrosis and cell senescence, although no difference was noted in the mature form of miR-1468 between healthy and COVID-19-diseased cardiac tissue [101].
T277 17961-18139 Sentence denotes TGF-β1 plays a key role in fibrosis-related pathologies including cardiac fibrosis, and, furthermore, miR-1468 activates non-canonical TGF-β1 and MAPKs signalling pathways [101].
T278 18140-18659 Sentence denotes Moreover, miR-1468-5p expression has been found to be upregulated in regulatory T cells, which have a significant role in autoimmune disorders, transplant rejection, allergic diseases, and asthma [102]. miR-1468-5p has previously been associated with glioma, where it inhibits growth and cell cycle progression by targeting ribonucleotide reductase large subunit M1 (RRM1), based on a study on patients from the Chinese Glioma Genome Atlas [103]. miR-1468-5 is also linked to progressing hepatocellular carcinoma [104].
T279 18660-18793 Sentence denotes Interestingly, in Alzheimer’s disease, miR-1468-5p has been identified to be at lower abundance compared with healthy controls [105].
T280 18794-18920 Sentence denotes It has furthermore been identified as a biomarker in late seizure in patients with spontaneous intracerebral haemorrhage [49].
T281 18921-19029 Sentence denotes The link between miR-1468-5 in viral infection and other comorbidities will need to be further investigated.
T282 19030-19181 Sentence denotes miR-129-2-3p, here identified as a common mutated miR, has previously been identified as a regulator in human cancer development and progression [106].
T283 19182-19325 Sentence denotes It has been identified as a diagnostic and prognostic biomarker for renal cell carcinoma [107] and a suppressor of serous ovarian cancer [104].
T284 19326-19529 Sentence denotes Its upregulation suppresses breast cancer cell proliferation and induces its apoptosis, while downregulation, via hypermethylation, increases breast cancer progression due to BCL2L2 overexpression [107].
T285 19530-19776 Sentence denotes It furthermore attenuates cell migration and invasion in renal cell carcinoma by affecting the downregulation of various metastasis-related genes [108]. miR129-2 has been linked to a range of haematological malignancies, including lymphoma [109].
T286 19777-19913 Sentence denotes It is also linked to lung adenocarcinoma including regulation of cell proliferation [110], as well as to hepatocellular carcinoma [111].
T287 19914-20107 Sentence denotes Interestingly, miR-129-2-3p has been found to be upregulated in human papilloma virus-positive (HPV) head and neck squamous cell carcinoma [112] and in HPV transfected keratinocyte cells [113].
T288 20108-20279 Sentence denotes In the light of increasing understanding of the link between SARS-CoV-2 and comorbidities, underlying changes in miR-129-2-3p expression may be of considerable importance.
T289 20280-20420 Sentence denotes A number of KEGG pathways have been strongly linked to the main miRs identified as being related to sequences within the SARS-CoV-2 genomes.
T290 20421-21237 Sentence denotes These include: “Mucin type O-glycan biosynthesis”, “TGF-β signalling pathway”, “Morphine addiction”, “Metabolism of xenobiotics by cytochrome P450”, “Other types of O-glycan biosynthesis”, “Vitamin digestion and absorption”, “Glycosaminoglycan biosynthesis—heparan sulfate/heparin”, “GABAergic synapse”, “Cytokine-cytokine receptor interaction”, “Signalling pathways regulating pluripotency of stem cells”, “Amphetamine addiction”, “Axon guidance”, “Hippo signalling pathway”, “Prolactin signalling pathway”, “mRNA surveillance pathway”, “Glycosphingolipid biosynthesis—lacto and neolacto series”, “Bile secretion”, “Circadian entrainment”, “N-glycan biosynthesis”, “Mismatch repair”, “Drug metabolism—cytochrome P450”, “Glutamatergic synapse”, “Glycosaminoglycan degradation”, “Antigen processing and presentation”.
T291 21238-21574 Sentence denotes The relevance of several of these KEGG pathways has been discussed above in direct relation to the various miRs and provides a novel insight into the putative interplay of these pathways and the microRNAs identified in COVID-19, and may also help in furthering understanding of the interplay of miRs, viral infections and comorbidities.